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Genomic Clustering Facilitates Nuclear Processing of Suboptimal Pri-miRNA Loci

Renfu Shang1, S Chan Baek2, Kijun Kim2

  • 1Department of Developmental Biology, Sloan Kettering Institute, 1275 York Ave, Box 252, New York, NY 10065, USA.

Molecular Cell
|April 18, 2020
PubMed

Insights

Microprocessor complex (Drosha/DGCR8) processing of weak miRNA substrates like mir-451 is enhanced by proximity to other miRNAs within operons. This finding explains miRNA operon evolution and retention.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • MicroRNA (miRNA) biogenesis is crucial for gene regulation.
  • The Microprocessor complex, containing Drosha and DGCR8, processes most miRNAs.
  • Some miRNAs, like mir-451, present unique processing challenges.

Purpose of the Study:

  • To investigate the regulation of Microprocessor complex activity.
  • To understand the role of miRNA clustering in biogenesis.
  • To explore the evolutionary advantage of miRNA operons.

Main Methods:

  • DGCR8 tethering assays were employed.
  • Operon structure-function assays were utilized.
  • Genomic analysis identified miRNA operons.
  • Experimental validation of selected operons was performed.

Main Results:

  • Dicer-independent mir-451, a weak Microprocessor substrate, requires clustering for efficient processing.
  • Local recruitment and transfer of Microprocessor complex enhances processing of suboptimal substrates.
  • Genomic analysis revealed enrichment of suboptimal canonical miRNAs in operons.
  • Several such operons were experimentally validated.

Conclusions:

  • Proximity-based enhancement of hairpin processing explains miRNA operon retention.
  • This mechanism may drive the evolutionary emergence of miRNA operons.
  • Clustering provides a regulatory layer for Microprocessor complex activity on specific miRNA substrates.
Keywords:
DGCR8DroshaMicroprocessormiR-451miRNA clustermicroRNA

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